The invention discussed and claimed within relates to the epimerization of sugars, and in particular epimerization of aldoses. Even more particularly it relates to solid catalysts which effect such epimerization under relatively mild condition, to the use of such catalysts in epimerizing aldoses, and to a continuous process of epimerizing sugars using a fixed bed of such catalysts.
Recently Bilik in Czechoslovak Certificate of Authorship No. 149,463 has reported that molybodic acid epimerizes aqueous solutions of L-mannose. Reactions conducted at 70.degree. to 95.degree. C. and a pH up to 7 were said to afford equilibrium mixtures of epimeric sugars within a reasonable time. However, Bilik later observed that the epimerization rate of mannose was 20 times slower at pH 5.9 than at 2.9, and that for glucose was 5 times slower, demonstrating that a highly acidic medium is desirable for the epimerization; Bilik and coworkers, Chem. Abst., 89(19): 163846m (1978). Independently we have observed that a highly acidic medium of pH between about 1 and 3 is necessary to effect epimerization at a reasonable rate with amounts of soluble molybdate under about 1500 ppm relative to aldose. U.S. Pat. No. 4,718,405. The latter limitation on the amount of soluble molybdate used is a consequence of commercial reality. Mechanistic studies on the epimerization have been performed by Hayes et al. (J. Amer. Chem. Soc., 104,6764 (1982)) in aqueous solution at a pH of 4.5 and at 90.degree. C. using approximately 30,000 ppm soluble molybdenum relative to aldose.
The procedure of Bilik is valuable insofar as it epimerizes aldoses to an equilibrium mixture without the formation of substantial amounts of byproducts, including color bodies. The epimerization of aldoses is desirable not only in the preparation of relatively rare sugars, such as L-ribose from L-arabinose and 6-deoxy-L-glucose from L-rhamnose, but also in altering the product mixture in sugar syntheses. For example, L-sugars, including L-glucose, have potential as non-nutritive sweeteners, and the preparation of L-glucose is attended by formation of L-mannose. Although separation of L-glucose from L-mannose can be effected in various ways, the presence of mannose in the separation feedstock increases the cost of the purified L-glucose, with its cost increasing with increasing mannose content in the feedstock. Unfortunately, a mixture of L-glucose and L-mannose generally is produced under kinetic control with the L-mannose in preponderance, which imposes heavy cost penalties upon the production of relatively pure L-glucose. Since glucose is thermodynamically favored relative to mannose (Hayes et al.,op. cit.) it follows that if the separated mannose or the kinetically formed product were equilibrated substantial and quite significant reductions it cost would accrue.
However valuable may be the use of soluble molybdate as an epimerizing reagent it still presents stubborn disadvantages in a commercial process. In particular, soluble molybdate requires as a practical matter highly acidic (pH less than about 3.0) solutions for epimerization. Depending on the aldose epimeric pair such a low pH can be vexing in causing side reactions affording unwanted products. The use of a soluble molybdate as an epimerizing reagent also requires an additional processing step to later remove it from solution. Where the epimeric pair is separated frequently it is necessary to remove the molybdate prior to the separation stage, but in any event it would be quite unusual for any industrial use of an aldose to tolerate significant amounts of molybdate in the product. Finally, the use of a soluble molybdate makes it difficult to tailor a continuous epimerization process which often is preferable to a batch process.
What is needed is an epimerization catalyst which operates under heterogeneous reaction conditions, i.e., a solid epimerization catalyst. What is needed is a solid epimerization catalyst which operates at a pH indigenous to aqueous solutions of aldoses, which is normally in the pH range of 4-6. What is needed is a solid epimerization catalyst which remains stable while exhibiting activity at a mildly acidic pH. What is needed is a stable, selective epimerization catalyst operative under only mildly acidic conditions and whose active component is not leached from the catalyst to any significant extent under normal reaction conditions. What we provide is just such a catalyst.
In particular, we have found that strong anion exchange resins whose exchangeable sites are occupied by molybdate are quite active in epimerizing aldoses with high selectivity under mildly acidic conditions. Quite surprisingly, solid catalysts can be made from which less than 50 ppm molybdenum, and often under 10 ppm molybdenum, leached into the epimerized aqueous mixture. The activity of such catalysts in continuous operation remains high through more than 320 hrs. of operation. A process for continuous epimerization based on such solid catalysts is readily devised, successfully practiced, and is economically rewarding, and has the further advantage of effecting isomerization at a pH indigenous to the aqueous solutions of the aldose being isomerized, leading to reduced incidence of undesired side reactions and byproducts.
The low level of molybdenum leach from a solid epimerization catalyst as attained in our invention is an indispensable prerequisite for commercial acceptability of such a catalyst and for commercial success of a continuous epimerization process based on such a catalyst. At the low leach levels characteristic of our process it may not be necessary to require a separate step for molybdenum removal, thereby obviating a unit process in a manufacturing procedure. Although a low molybdenum leach level does not per se ensure prolonged catalyst life, a low leach level is a necessary requirement for high catalyst life with low activity loss since continued removal of molybdenum from the catalyst is tantamount to continued removal of the catalytically active species which must invariably lead to deterioration of catalyst performance.
In U.S. Pat. No. 4,029,878 Kruse disclosed that mannose yield in the epimerization of glucose with a hexavalent molybdenum catalyst is enhanced by using a solution containing at least 50% by weight glucose. The patentee typically used a solution of hexavalent molybdenum at a concentration of at least 0.125 weight percent molybdic acid, and added a mixed bed ion exchange resin after reaction was complete, presumably to remove, or reduce, soluble molybdenum. However, in two cases extraordinarily high levels of molybdic acid (0.83 and 1.67 weight percent) were used in conjunction with an anion exchange resin, but in these cases mannose yield appear less than what could be expected to be observed in the absence of the resin.
In Japanese laid-open application No. 55-76894, the inventors found that an epimerization catalyst of molybdenum-exchanged anion exchange resin identical to that of Kruse rapidly lost activity, their data showing that mannose yields at 90.degree. C. dropped from 30% to under 15% within 35 hours. Largely as a result of this rapid deactivation the workers developed "Mo-type ion-exchange fibers" which could be used as an epimerization catalyst. The nature of this catalyst is not clear. However, a distinction which will be seen to be critical is that these workers exchanged molybdenum under basic conditions, whereas in the present invention it will be seen to be essential to perform the exchange at a rather acidic pH. Although the paucity of description makes the nature of their catalyst and process uncertain, what does seem certain is that the Japanese process fails to demonstrate the low Mo leach levels or the high stability of our catalyst, both essential features of our process.